Study On The Coupling Process Of Separation-preparation And Application Of Yixintong Sustained-release Capsule

In this paper, the coupling process of separation-preparation wasinvestigated. High content of amino group chitosan adsorbent has beenprepared through inverse suspension method and chemical cross-linkingmethod, flavonoids which are isolated from the leaves of Crataeguspinnatifida Bge.var. major N.E.Br. as the adsorbed model. Adsorptionconditions and adsorption mechanism were investigated. Then, thesustained -release preparations were prepared directly, and sustained-release conditions were investigated.1. The amined porous chitosan microspheres were prepared throughinverse suspension method. The structure of the micorsphere wascharacterized by scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR).The results indicated that the ratio of waterand liquid paraffin was 1:1, concentration of chitosan was 2%, moleculeweight was 50 Da, degree of deacetylation was 95%, dosage offormaldehyde was 2.90 ml, dosage of epichlorohydrin was 1.95 ml,agitating speed was 350 r/min, dosage of quadrol was 2 ml, the adsorbenthad high adsorption capacity on flavonoids.The adsorption condition was optimized by orthogonal design, thebest optimal condition as follows: pH 6.0, temperature 30℃, solutionconcentration was 3.71 mg/ml, the adsorption capacity reached 645.5mg/mg.The equilibrium isotherm was correlated by the Langmmuirequation and Freundlich equation respectively. Mechanism of adsorptionfor flavonoids was presumed by analyzing the IR. The static electricity,hydrogen bond might be the main force.2. The chitosan gel was prepared through chemical cross-linking method,and prepared condition was investigated. The chitosan powder wasmodified through phase change (CTS), then, the chitosan gel wascross-linked with glutaraldehyde, reaction temperature 20℃, time was 30min, dosage of glutaraldehyde was 0.5 ml. Then, cross-linked gel wasactivated by epichlorohydrin, time 1.5 h, temperature was 60℃,dosageof epichlorohydrin was 1.95 ml. Finally, it was reacted with quadrol.The adsorption condition was optimized by orthogonal design, thebest optimal condition as follows: pH 6.5, temperature 30℃, solution concentration was 3.18 mg/ml, the adsorption capacity reached 618.8mg/mg. The equilibrium isotherm was correlated by the Langmuirequation-Freundlich equation respectively.3. The mass fraction of adsorbed flavonoids from adsorbents prepared byinverse suspension method and chemical cross-linking method weremeasured, the results showed that the percentage was more than 77%.The effects of release medium, revolving speed, degree ofdeacetylation, molecule weight were considered. The results showed thatthe release medium of 30% ethanol in the first 4 hours, 0.5 mol/L NaClin the later 8 hours, the revolving speed was 100 r/min, the accumulativerelease degree of tablets were 74.1% and capsules were 71.1%respectively. Compared with normal tablets, the sustained-releasepreparation had obviously prolonged effect. The curve of cumulativesustained-release was accorded with the Higuchi equation and Peppasequation, which were explained by non-Fickian perfusion. Both diffusionand erosion were involved during the period of release.